The experiments outlined in this proposal will investigate the neural pathways through which visceromotor responses to stress are mediated. In addition, differences in neural activation following acute versus repeated exposure to a stress will be examined. These studies will provide insight into how the brain processes stress, an important concept in that stress is a risk factor thought to be associated with a number of pathophysiological states such as memory deficit, depression and anorexia. Responses to a neurogenic stress (one that involves a degree of conscious interpretation), rather than to a systemic stress (one that is predominantly reflexive with little activation of higher brain regions), will be tested. The model of choice in this proposal is restraint, a model that is well established in the literature. Restraint also is likely to more closely approximate the type of stress experienced by humans, as opposed to other neurogenic stressors that have a greater pain component such as foot shock or immobilization. Retrograde tracers will be used to identify cells in the brain and brainstem that project to the paraventricular nucleus of the hypothalamus, a region capable of integrating endocrine, neuroendocrine and autonomic responses to homeostatic challenges. Immunohistochemical localization of Fos will demonstrate cells activated by either 1 or 14 days of restraint. Changes in specific effectors of the hypothalamic-pituitary-adrenal axis, the main system responsive to stress, will be measured by quantitative in situ hybridization